NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Hope Johnson (PM 2 1 ), 703

- 30 5

- 5410

. Arysta LifeScience North America, LLC [Insert petition number]
Summary of Petitions EPA has received a pesticide petition ([insert petition number]) from Arysta LifeScience North America, LLC 15401 Weston Parkway, Suite 150, Cary, North Carolina 27513 proposing, pursuant to section 408(d) of the Federal Food, Drug, a nd Cosmetic Act (FFDCA), 21 U.S. C . 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of Fluoxastrobin, [ ( 1 E)

- [2

- [[6

- (2

- chlorophenoxy)

- 5

- fluoro

- 4

- pyrimydinyl]oxy]phenyl] (5,6 dihydro

- l,4,2

- dioxazin

- 3

- yl)methanone O

- methyloxime, and its Z isomer, ( 1 Z)

- [2

- [[6

- (2 chlorophenoxy)

- 5

- fluoro

- 4

- pyrimydinyl] oxy]phenyl] (5,6

- dihydro

- l,4,2

- dioxazin

- 3 yl)methanone O

- methyloxime ] in or on the raw agricultural commodities avocado at 0.9 parts per million (ppm); barley, grain at 0.4 ppm; barley, hay at 15 ppm; barley, straw at 15 ppm; Rapeseed subgroup 20A at 0.8 ppm; and Dried shelled pea and bean (except soybean) subgroup 6C at 0.2 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granti ng of the petition. Additional data may be needed before EPA rules on the petition.
A. Residue Chemistry 1. Plant metabolism. The metabolism of fluoxastrobin in plants is adequately understood as published in the Federal Register of April 23, 2003 ( 68 FR19991 ) . Studies have been conducted to delineate the metabolism of radiolabeled fluoxastrobin in peanut, tomato, spring wh eat, and various representative rotational crops, all showing similar results. The residue of concern is parent fluoxastrobin (sum of E and Z isomer).

2. Analytical method

. Adequate analytical methodology is avai lable for enforcement purposes. The method comprises microwave solvent extraction followed by a solid phase extraction clean up and quantification by high performance liquid chromatography with tandem mass spectrometric detection (HPLC/MS/MS). The individual detector responses for measu red E

- and Z

- isomers is summed to give total residue. The validated limit of quantitation is 0.01 ppm for all matrices

.
3. Magnitude of residues

. Avocado A total of 5 field trials were conducted in the United States, EPA Region 10 in order to evaluate the magnitude of fluoxastrobin, ( E

- isomer and Z

- isomer) residues in a vocado. The number and geographic locations of field trials fulfill the US EPA requirements for a regional (Region 10) registration on avocado.

Page 1 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The Evito ® 480 SC Fun gicide formulation was applied three times using airblast application at the maximum proposed label use rate of 0.21 lb ai/A/ application

. The spray volumes ranged from 73 to 75 gallons per acre (GPA) (683 to 711 l/ha) for concentrate spray volumes and 150 to 244 GPA (1403 to 2282 l/ha) for dilute spray volumes. Non

ionic surfactants (NIS) labeled for agricultural use were added to the spray mixtures. The applications were made with a 14

- day interval between applications, to support a Region 10 registration based on a 7

- day pre

- harvest interval (PHI)

. S amples were collected from both control and treated plots for analysis at normal harvest.
Apparent residues of each analyte were below the LOQ in/on all non

- treated control samples of avocado RAC samples. No interferences were noted in control samples. Residues were not corrected for procedural recovery results. Total residues ( E

- isomer + Z

- isomer) ranged from 0.029 to 0.549 ppm (mean = 0.178 ± 0.164, n = 10).
The maximum storage interval from collection to extraction for analysis was 259 days for avocado fruit. Fluoxastrobin ( E

- isomer and Z

- isomer) freezer storage stability has been demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), potato (tuber), tomato (fruit), and lettuce (head) for 30 months

. Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on A vocad o is proposed at 0.9 ppm. Barley A total of 12 barley trials were established in the U. S. Trials were established in EPA Regions 2 (one trial), 5 (three trials), 7 (four trials), 9 (one trial), 10 (one trial), and 11 (two trials). Trials were conducted on soil types and under cultural practices typical for commercial barley production. The number and geographi c locations of field trials fulfill the requirements for registration on barley as set forth in the Residue Chemistry Test Guidelines, O PPTS 860.1500 (Crop Field Trials) and OPPTS 860.1520 (Processed Food/Feed) and will fulfill the EPA 40 CFR 158 requirements for registration of pesticides.
The treated plots received two foliar broadcast applications of Evito® 480 SC Fungicide at 0.125 lb ai/A/application (equal to 0.140 kg ai/ha/application) ±5%. The applications were made nominally in 10 gal/A (GPA) ± 10% of spray mix (93.5 L/ha) using foliar broadcast ground spray equipment, and a non

- ionic surfactant (≥80% ai) at label use rate was ad ded to the spray mixtures. Applications were made when the crop was nominally at BBCH 37

- 39 (~80

- 100% flag leaf emergence) and then 14 ± 1 days after the first application. Treated barley hay RAC samples were cut 7 ± 1 days after last application (DALA) at all sites
Total residues ( E

- isomer + Z

- isomer) in barley hay, grain, and straw RACs ranged from 1.10 to 10.1 ppm (mean = 4.97 ± 2.36, n = 24); 0.00749 to 0.281 ppm (mean = 0.0758 ± 0.0712, n = 24); and 0.133 to 10.1 ppm (mean = 2.05 ± 2.60, n = 24), respectively.

Page 2 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The barley hay decline data indicate that E+Z

- isomer fluoxastrobin residues (corrected for % moisture) decrease over the 19

- day sampling period with a calculated half

- life of 6.3 days (R 2 = 0.9611). The barley grain decline data indicate tha t E+Z

- isomer fluoxastrobin residues (corrected for % moisture) decrease over the 20

- day sampling period with a calculated half

- life of 12.6 days (R 2 = 0.9835). The barley straw decline data indicate that E+Z

- isomer fluoxastrobin residues (corrected for % moisture) decrease over the 20

- day sampling period with a calculated half

- life of 13.0 days (R 2 = 0.9749).
The barley RAC samples were stored frozen (below freezing at the field sites and typically at ≤

- 10 oC at the analytical laboratory) for a maximum of 196 days from collection to extraction for analysis. Barley processed commodities were analyzed within 29 days of processing; therefore, freezer storage stability data are not required (OPPTS 860.1380). Fluoxastrobin ( E

- isomer and Z

- isomer) freezer storage stability has been demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), potato (tuber), tomato (fruit), and lettuce (head) for 30 months

. Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on B arley, grain at 0.4 ppm; B arley, hay at 15 ppm; and B arley, straw at 15 ppm.
Canola (Rapeseed Subgroup 20A) Seventeen canola trials were established in the U. S. and Canada in 2014. Trials were established in NAFTA Regions 2 (one trial), 5 (two trials), 7 (two trials), 11 (three trials), and 14 (nine trials). Trials were conducted on soil types and under cultural practices typical for commercial canola production. The number and geographi c locations of field trials fulfill the requirements for registration on canola as set forth in the Residue Chemis try Test Guidelines, OPPTS 860.1500 (Crop Field Trials), OPPTS 860.1520 (Processed Food/Feed), PMRA DIR98

- 02, and PRMA DIR 2010

- 05 requirements for registration of pesticides.
The treated plots received two foliar broadcast applications of Evito® 480 SC Fu ngicide at 0.15 lb ai/A/application (equal to 0.168 kg ai/ha/application) (±5%) applied nominally 28 (27 to 30

- day range) and 21 (20 to 22

- day range) days before harvest (DBH). The applications were made nominally in 10 gal/A (GPA) ± 10% of spray mix (93. 5 L/ha) using foliar broadcast ground spray equipment, and a non

- ionic surfactant (≥80% ai) at label use rate was added to the spray mixtures.
Total residues ( E

- isomer + Z

- isomer) in canola seed RAC ranged from 0.0115 to 0.587 ppm (mean = 0.161 ± 0.138, n = 34). A comparison of the residues in the RAC with those in the canola meal and refined oil indicated that the residues do not concentrate (processing factors ≤1) in the processed commodities.

Page 3 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

The canola RAC samples were stored frozen (below freezing a t the field sites and typically at ≤

- 10 oC at the analytical laboratory) for a maximum of 145 days from collection to extraction for analysis. Fluoxastrobin ( E

- isomer and Z

- isomer) freezer storage stability has been demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), potato (tuber), tomato (fruit), and lettuce (head) for 30 months

. Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on C anola (Rapeseed Subgroup 20A) is proposed at 0. 8 ppm. Dried Shelled Bean & Dried Shelled Pea (Crop Subgroup 6C) Eleven dried shelled pea and thirteen (two extra trials were completed) dried shelled bean trials were completed in the U. S. and Canada. Trials were conducted on soil types and under cultural practices typical for commercial dried shelled pea and dried s helled bean production. Dried shelled pea trials were established in NAFTA Regions 7 (three trials), 11 (five trials), and 14 (three trials). Dried shelled bean trials were established in NAFTA Regions 5 (four trials), 7 (two trials), 7a (one trial), 8 ( one trial), 9 (one trial), 10 (one trial), 11 (one trial), and 14 (two trials). The number and geographic locations of field trials will fulfill the requirements for registration on dried shelled pea and dried shelled bean (Crop Subgroup 6C) as set forth in the Residue Chemistry Test Guidelines, OPPTS 860.1500 (Crop Field Trials) and Canadian PMRA Directive 2010

- 05 and fulfill the EPA 40 CFR 158 requirements for registration of pesticides. The treated plots received two foliar broadcast applications of Evi to® 480 SC Fungicide at 0.15 lb ai/A/application (equal to 0.168 kg ai/ha/application) ± 8.7% applied nominally 21 (19 to 24

- day range) and 14 (13 to 18

- day range) days before harvest (DBH), except for Trial

- 10 which made the applications 14 and 7 DBH. T he applications were made in 9.3 to 13.6 gal/A (GPA) of spray mix (87

- 127 L/ha) using foliar broadcast ground spray equipment, and a non

- ionic surfactant (≥80% ai) at label use rate was added to the spray mixtures.

Total residues ( E

- isomer + Z

- isomer) in dried shelled bean and dried shelled peas RACs ranged from <LOD to 0.146 ppm (mean = 0.0176 ± 0.0300, n = 26) and <LOQ to 0.148 ppm (mean = 0.0347 ± 0.0366, n = 22), respectively.
The dried shelled bean and dried shelled pea RAC samples were stored frozen (below freezing at the field sites and typically at ≤

- 10 oC at the analytical laboratory) for a maximum of 299 days from collection to extraction for analysis. Fluoxastrobin ( E

isomer and Z

- isomer) freezer storage stability has been demonstrated in a variety of crop matrices including wheat (forage, grain, and straw), potato (tuber), tomato (fruit), and lettuce (head) for 30 months , in canola seed for at least 152 days, and in c anola meal and refined oil for 151 days. These data indicate that fluoxastrobin residues are stable in frozen storage for the time periods encountered in this study.

Page 4 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

Based on the results of the above residue trials, a tolerance for fluoxastrobin in or on Dried Shelled Pea and Bean ( Crop Subgroup 6C ) is proposed at 0. 2 ppm.

B. Toxicological Profile The complete toxicity profile of fluoxaztrobin was previously published in the Federal Register of April 23, 2003 ( 68 FR19991 )

.
1. Acute toxicity. Oral and dermal LD 50 values were >2000 mg/kg bw. Inhalation LC 50 values were >4998 mg/ m 3 air. Fluoxastrobin technical was not irritating to rabbit skin, was moderately irritating to eyes in rabbits and was non

- sensitizing dermally in the Magnusson/Kligman maximization test in guinea pigs. Acute toxicity studies for fluoxastrobin technical support an overall tox icity Category III
2. Genotoxicty. Several genotoxicity tests were conducted to test for point

- mutagenic activity, chromosome aberration in vitro and in vivo, and for DNA repair. All tests conducted were negative, indicating no evidence of mutagenic or g enotoxic potential.
3. Reproductive and developmental toxicity. [An oral developmental toxicity study in rat did not reveal any evidence of teratogenic potential The maternal NOAELwas300mg/kg and the developmental NOAEL was 1000 mg/kg bw/day. An oral developmental toxicity study in rabbits demonstrated a maternal NOAEL of 25 mglkg bw/day, a developmental NOAEL of 1 00 mglkg bwlday and did not reveal any teratogenic potential. A two

generation study in rats, with a parental toxicity NOAEL of 73. 7mg/kgbw /day for males and 86.7 mglkgbw/day for females, did not reveal evidence of a primary reproductive toxicity potential. The reproductive NOAEL was 763.6 mg/kg bw/day for males and 806.5 mg/kg bw/day in females.

4. Subchron ic toxicity

. A subchronic toxicity feeding study with rats over 90 days demonstrated a NOAEL of 7.3 and 18.3 mg/kg bw/day for males and females, respectively, based on reduced body weights an d alterations in several urinary ' tract related clinical chemistry parameters, at the higher dose levels. In a subchronic feeding study in mice over 14 weeks a NOAEL was not established based on decreased alanine aminotransferase (ALA T) and increased absolute and relative liver weights at the low dose level (21. 7 and 35.3 mg/kg bw/day for males and females, respectively). A 14

- weekfeeding study in dogs demonstrated a NOAEL of 3.0 mg/kg bw/day based on decreased body weights and food consumption, and liver effects (enzyme induction, incr eased liver weights and cytoplasmic change) and thyroid effects (decreased T3).
5. Chronic toxicity. A 24

- month chronic/oncogenicity feeding study in rats demonstrated a NOAEL of 53.0 and 35.2 mg/kg bw/day for males and females, respectively. An oncogeni city study in the mouse revealed a NOAEL of 18.5 and 29.5 mg/kg bw/day for males and females, respectively based on liver effects. There was no indication in the rat or mouse for an oncogenic effect of fluoxastrobin. A one

- year feeding study with dogs demo nstrated a NOAEL of l. 7 and 1. 5 mg/kg bw/day for males and females, respectively, based on decreased body weights and slight liver effects (increased alkaline phospha tase (Aph) and liver weights).

Page 5 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

6. Animal metabolism

. Metabolism and pharmacokinetic studi es in the rats, lactating goats and laying hens demonstrate that fluoxastrobin residues are rapidly absorbed, metabolized and eliminated. There was no evidence of accumulation of residues in any tissues or organs. The metabolic pattern was always complex a nd numerous metabolites were identified. The main metabolic reactions, however, are very comparable for all tested animal species and most metabolites were present at low levels. As per the meat and milk tolerances established in40 CFR 180.609, the tolera nce expression includes fluoxastrobin (sum of E and Z isomers) and its phenoxy

- hydroxypyrimidine metabolite.]
7. Metabolite toxicology. The residues of concern are fluoxastrobin and its phenoxy

hydroxypyrimidine metabolite. This metabolite was investigated for acute oral toxicity and point mutagenic activity in a bacterial reverse mutation assay. The phenoxy

hydroxypyrimidine metabolite did not show mutagenic activity in the reverse mutation assay and the oral LD 50 w as >300<500 mg/kg body weight.
8. Endocrine disruption. There is no evidence to suggest that fluoxastrobin has any primary endocrine disruptive potential. Reproductive and developmental findings provided no evidence of an enhanced sensitivity of the young.

C. Aggregate Exposure 1. Dietary exposure. i. Food. A chronic dietary analysis was conducted to estimate exposure to fluoxastrobin residues in/on peanuts and peanut oil, refined, at the proposed higher tolerance values in addition to tolerances expected or established for all currently proposed and registered crop
uses. Acute analyses were not conducted since, as per EPA's 1/24/05 human health risk assessment, there was no indication of an adverse effect attributable to a single dose and therefo re an acute reference dose (aR f D) was not established. Tier I analysis was conducted for the chronic scenario using the D EEM

- FCID TM software. Chronic dietary exposure estimates from potential residues of fluoxastrobin for the US Population was 3 0 .5 % of the chronic R f D. The sub

- population with the highest exposure was “all infant (<1 year old)” with 84.9 % of the chronic R f D used. The Tier I assessment utilizes experimentally derived and default processing factors, and 100% crop treated information for all registered and proposed uses combined . These can be considered very conservative estimates of exposure

ii. Drinking water

. Drinking water was incorporated directly into the DEEM dietary assessment under “drinking water” for both “direct” and “indirec t” sources using the fluoxastrobin the post

- breakthrough average concentration modeled for turf which was higher than the concentration of 93 ppb that had been previously used in the dietary risk assessment. As such, the Tier 1 modeled groundwater concen tration of 137 ppb was used for drinking water in the chronic dietary risk assessment.
iii. Aggregate Exposure: No acute aggregate risk assessment was conducted since there was no acute endpoint of concern identified.

Page 6 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

Short

- term aggregate risks include dietary and non

- dietary sources of exposure. The only short

- term non

- dietary exposure comes from the potential for post

- application oral ingestion (hand

- to

- mouth activities) by children and inhalation exposure to adults during hand

- dispersal of granules when treating ornamentals.
The aggregation involved combining residential exposures with the appropriate chronic dietary exposure for children, 1

- 2 years old (MOE = 113) and the general US population (MOE = 602)

. T he se aggregate MOEs for adults and children are higher than the required 100, indicating acceptable short

- term aggregate risks. Long

- term aggregate risks are not needed since the residential use pattern for this product is not expected to result in residential handler or post

- application exposure of more than 6 months out of the year.

2 Non

- dietary exposure. Post

- application risks to the new proposed crops were assessed using transfer coefficients from EPA Policy 3 with the maximum proposed application rates, eight hours of exposure, and the default assumption of 25% of the application rate is available for dislodging. Because there is no short

- term dermal point of departure, only intermediate

- term risks were assessed.

Post

- application intermediate

- term derm al exposures and risks range from MOEs of 1,600 for hand

- harvesting avocados and moving irrigation pipe in dried peas and beans to over 50,000 for hand

- weeding barley indicating acceptable re

- entry risks for agricultural workers.
D. Cumulative Effects Fluoxastrobin is a novel strobilurin analog. Arysta LifeScience North America, LLC will submit information, if necessary, for EPA to consider concerning potential cumulative effects of fluoxastrobin consistent with the schedule established by EPA at 62 Fede ral Register 42020 (Aug. 4, 1997) and other EPA publications pursuant to the Food Quality Protection Act.
E. Safety Determination 1. U S P opulation. Using the conservative assumptions described above, based on the completeness and reliability of the toxicity data, it is concluded that dietary exposure (food and water) from the proposed and registered uses of fluoxastrobin will utilize at most 30.5% of the reference dose for the US Population, and is likely to be much less as more realistic data an d models are developed. EPA generally has no concern for exposures below 100% of the R f D because the R f D represents the level at or below which daily dietary (food plus water) exposure over a lifetime will not pose appreciable risks to human health. In add ition, aggregate (food and water dietary plus residential) MOEs are greater than 100 for adults for both short

- and intermediate

- term exposure durations. Finally, all handler exposure scenarios also have MOE greater than 100. Therefore, there is a reasonabl e certainty that no harm will occur to the US Population from aggregate exposure to

Page 7 of 8NOF Fluoxastrobin Petition for Tolerance in or on Avocado, Barley, Canola (Rapeseed Subgroup 20A), and Dried Shelled Pea and Bean (Crop Subgroup 6c)

fluoxastrobin.

2. Infants and children. Consideration of the toxicology database as described above leads to no additional concerns for infants and children. Therefore th e FQPA safety factor can be established at 1 X

. All post

- application risks for both adults and children exceeded 100, indicating acceptable risks. The lowest children’s oral short

- term MOE was 180 based on hand

- to

- mouth activities in turf treated with a liquid formulation; this value was used in the sh ort

- term aggregate risk assessment.

F. International Tolerances

. Codex maximum residue levels (MRLs) are not yet established for fluo xastrobin.

Page 8 of 8